LAS VEGAS —
“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.
cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.
Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.
The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.
cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.
The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
An ‘Intriguing’ Method
During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.
Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.
“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.
Weill Cornell Medical College
Dr. Dana Lukin
He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.
He also called for prospective studies to validate the approach.
If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.
Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..